title: miR-195 competes with HuR to modulate stim1 mRNA stability and regulate cell migration.
abstract: Stromal interaction molecule 1 (Stim1) functions as a sensor of Ca2+ within stores and plays an essential role in the activation of store-operated Ca2+ entry (SOCE). Although lowering Stim1 levels reduces store-operated Ca2+ entry and inhibits intestinal epithelial repair after wounding, the mechanisms that control Stim1 expression remain unknown. Here, we show that cellular Stim1 abundance is controlled posttranscriptionally via factors that associate with 3'-untranslated region (3'-UTR) of stim1 mRNA. MicroRNA-195 (miR-195) and the RNA-binding protein HuR competed for association with the stim1 3'-UTR and regulated stim1 mRNA decay in opposite directions. Interaction of miR-195 with the stim1 3'-UTR destabilized stim1 mRNA, whereas the stability of stim1 mRNA increased with HuR association. Interestingly, ectopic miR-195 overexpression enhanced stim1 mRNA association with argonaute-containing complexes and increased the colocalization of tagged stim1 RNA with processing bodies (P-bodies); the translocation of stim1 mRNA was abolished by HuR overexpression. Moreover, decreased levels of Stim1 by miR-195 overexpression inhibited cell migration over the denuded area after wounding but was rescued by increasing HuR levels. In sum, Stim1 expression is controlled by two factors competing for influence on stim1 mRNA stability: the mRNA-stabilizing protein HuR and the decay-promoting miR-195.
authors.affiliation: Department of Surgery, Cell Biology Group, University of Maryland School of Medicine, MD 21201, USA, Baltimore Veterans Affairs Medical Center, Baltimore, MD 21201, USA, Department of Pathology, University of Maryland School of Medicine, MD 21201, USA and Laboratory of Genetics, National Institute on Aging-IRP, NIH, Baltimore, MD 21224, USA.
authors.forename: Ran
authors.initials: R
authors.lastname: Zhuang
authors.forename: Jaladanki N
authors.initials: JN
authors.lastname: Rao
authors.forename: Tongtong
authors.initials: T
authors.lastname: Zou
authors.forename: Lan
authors.initials: L
authors.lastname: Liu
authors.forename: Lan
authors.initials: L
authors.lastname: Xiao
authors.forename: Shan
authors.initials: S
authors.lastname: Cao
authors.forename: Natasha Z
authors.initials: NZ
authors.lastname: Hansraj
authors.forename: Myriam
authors.initials: M
authors.lastname: Gorospe
authors.forename: Jian-Ying
authors.initials: JY
authors.lastname: Wang
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000235:genetics*; D051959:ELAV Proteins / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D035683:MicroRNAs / Q000378:metabolism*; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D000071737:Stromal Interaction Molecule 1
chemical_list: D020413:3' Untranslated Regions; D051959:ELAV Proteins; C584139:MIRN195 microRNA, rat; D008562:Membrane Glycoproteins; D035683:MicroRNAs; D012333:RNA, Messenger; C518857:Stim1 protein, rat; D000071737:Stromal Interaction Molecule 1